Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576.
Department of Otolaryngology, Singapore General Hospital, Duke-NUS Graduate Medical School, Singapore 169608.
Anal Chem. 2021 Feb 2;93(4):2053-2061. doi: 10.1021/acs.analchem.0c03778. Epub 2021 Jan 6.
Recurrent nasopharyngeal carcinoma (NPC) is the main cause of poor prognosis for NPC patients after chemo- and radiotherapies. Subsequent long-term follow-ups of post-treatment patients are crucial for the early discovery of tumor recurrence with timely intervention. Current clinical imaging methods based on tissue morphology encounter difficulties in differentiating recurrent tumors from post-treatment inflammation and fibrosis. In this work, we apply a unique fiberoptic Raman endoscopy technique to address the challenges for label-free follow-up surveying of post-treatment NPC patients and accurate detection of tumor recurrence. Significant Raman spectral differences can be observed among normal, NPC, and nonrecurring post-treatment patients. Raman endoscopy provides diagnostic accuracy of 100% for detecting recurrent NPC from early post-treatment inflammation and diagnostic accuracy of 98.21% for separating recurrent NPC from long-term post-treatment fibrosis. Further quantitative Raman modeling on nasopharyngeal tissue Raman data acquired unveils the changes of major tissue biochemicals (e.g., triolein, elastin, keratin, fibrillar collagen, and type IV collagen) associated with primary NPC and post-treatment recurrent NPC tissue compared to normal nasopharyngeal tissue. This work demonstrates that fiberoptic Raman endoscopy can be a clinically powerful diagnostic tool for rapid, label-free post-treatment surveying and recurrent tumor detection in NPC patients at the molecular level.
复发性鼻咽癌(NPC)是化放疗后 NPC 患者预后不良的主要原因。对治疗后患者进行长期随访对于早期发现肿瘤复发并及时干预至关重要。目前基于组织形态学的临床影像学方法在区分复发性肿瘤与治疗后炎症和纤维化方面存在困难。在这项工作中,我们应用独特的光纤 Raman 内窥镜技术,解决了治疗后 NPC 患者无标记随访调查和肿瘤复发准确检测的挑战。正常、NPC 和非复发性治疗后患者之间可以观察到明显的 Raman 光谱差异。Raman 内窥镜对早期治疗后炎症中复发性 NPC 的检测具有 100%的诊断准确率,对长期治疗后纤维化中复发性 NPC 的检测具有 98.21%的诊断准确率。对从正常鼻咽组织、原发性 NPC 组织和治疗后复发 NPC 组织中获得的鼻咽组织 Raman 数据进行定量 Raman 建模,揭示了与原发性 NPC 和治疗后复发 NPC 组织相关的主要组织生物化学物质(如三油酸甘油酯、弹性蛋白、角蛋白、纤维胶原和 IV 型胶原)的变化。这项工作表明,光纤 Raman 内窥镜可以成为一种强大的临床诊断工具,用于 NPC 患者在分子水平上进行快速、无标记的治疗后调查和复发性肿瘤检测。